ethyl 2-(7-bromo-3,4-dihydro-2H-1,4-benzothiazin-3-yl)acetate -Drug Synthesis Database

【结构式】

【分子编号】25186

【品名】ethyl 2-(7-bromo-3,4-dihydro-2H-1,4-benzothiazin-3-yl)acetate

【CA登记号】

【分子式】C₁₂H₁₄BrNO₂S

【分子量】316.2187

【元素组成】C 45.58% H 4.46% Br 25.27% N 4.43% O 10.12% S 10.14%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

Benzothiazin (III) was prepared by condensation of 2-aminothiophenol (I) with ethyl 4-bromoacetoacetate (II). Subsequent reduction of (III) with NaBH3CN provided (IV), which was brominated using N-bromosuccinimide to afford (V). This was coupled with ethyl oxalyl chloride to give amide (VI). Nitration of (VI) was then performed with HNO3 in H2SO4 at -10 C. Further reduction of the nitro group of (VII) with concomitant cyclization produced the tricyclic compound (VIII). After resolution by chiral preparative HPLC, the required (R)-enantiomer was hydrolyzed with NaOH to afford carboxylic acid (IX). This compound was finally isolated as the sodium salt upon treatment with aqueous NaHCO3, followed by lyophilization.

参考文献中间体

合成目标

【1】 Moretti, R.; Zimmermann, K. (Novartis AG); Quinoxaline-2,3-diones with an oxa or thiaheterocyclic fused ring. CA 2157231; EP 0705835; JP 1996109185 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11043	Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride	4755-77-5	C₄H₅ClO₃	详情	详情
(I)	25182	2-aminobenzenethiol	137-07-5	C₆H₇NS	详情	详情
(III)	25183	ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate	70-23-5	C₅H₇BrO₃	详情	详情
(IV)	25184	ethyl 2-[2H-1,4-benzothiazin-3(4H)-ylidene]acetate		C₁₂H₁₃NO₂S	详情	详情
(IV)	25185	ethyl 2-(3,4-dihydro-2H-1,4-benzothiazin-3-yl)acetate		C₁₂H₁₅NO₂S	详情	详情
(V)	25186	ethyl 2-(7-bromo-3,4-dihydro-2H-1,4-benzothiazin-3-yl)acetate		C₁₂H₁₄BrNO₂S	详情	详情
(VI)	25187	ethyl 2-[7-bromo-3-(2-ethoxy-2-oxoethyl)-2,3-dihydro-4H-1,4-benzothiazin-4-yl]-2-oxoacetate		C₁₆H₁₈BrNO₅S	详情	详情
(VII)	25188	ethyl 2-[7-bromo-3-(2-ethoxy-2-oxoethyl)-5-nitro-2,3-dihydro-4H-1,4-benzothiazin-4-yl]-2-oxoacetate		C₁₆H₁₇BrN₂O₇S	详情	详情
(VIII)	25189	ethyl 2-(9-bromo-5,6-dioxo-2,3,6,7-tetrahydro-5H-[1,4]thiazino[4,3,2-de]quinoxalin-3-yl)acetate		C₁₄H₁₃BrN₂O₄S	详情	详情
(IX)	25190	2-[(3R)-9-bromo-5,6-dioxo-2,3,6,7-tetrahydro-5H-[1,4]thiazino[4,3,2-de]quinoxalin-3-yl]acetic acid		C₁₂H₉BrN₂O₄S	详情	详情

Extended Information